Fig. 1. The HO-1 pathway and its effect on microbial infections.

Microbial infections that may involve the HO-1 pathway include those due to bacteria (polymicrobial, gram-positive, and gram negative); mycobacteria; fungi; viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), HIV (and its complication Kaposi’s sarcoma – KS), and influenza; and the parasitic species leading to malaria (both the exoerythrocytic liver stage and the erythrocytic blood stage). These microbes may lead to either disseminated disease (which may result in sepsis) or organ specific infections. Microbial infections typically lead to an induction of HO-1, which degrades heme generating carbon monoxide (CO), biliverdin-IXα (subsequently reduced to biliverdin-IXα, and iron. These metabolites have a number of properties including the anti-inflammatory and pro-phagocytic effects of CO, and the anti-oxidant and anti-inflammatory properties of biliverdin/bilirubin. The properties of HO-1, and the products of heme catabolism, then have an ability to suppress (−) the microbial response or promoter (+) microbial survival.